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Buerger’s Disease Revisited
Buerger's Disease Revisited STANFORD WESSLER, M.D.*
Thromboangiitis obliterans was originally described by Leo Buerger in 1908 and became firmly established along with atherosclerosis as one of the two major causes of peripheral arterial occlusive disease. Beginning in 1933, skepticism concerning the identity of thromboangiitis obliterans was expressed by several investigators. 25 . 26. 28. 43 An analysis of the entire experience with Buerger's disease at the Beth Israel Hospital in Boston from 1929 to 1956 was published in 1960, together with a review of the various considerations in the literature that had perpetuated thromboangiitis obliterans as an entity.82 It was concluded from this study that the disease originally described by Buerger was indistinguishable from atherosclerosis, systemic embolization, or peripheral arterial or venous thrombosis, singly or in combination. Because of the difficulties inherent in establishing a negative hypothesis, any attempt to prove that thromboangiitis obliterans did not then and does not now exist, can approach such a goal only asymptotically. Nevertheless, in 1960, the available evidence appeared to favor the view that Buerger's disease had never been and was not then an entity in either the clinical or the pathologic sense and that the term should be discarded. 82 The response to this recommendation was not large, but what did appear in print was vigorous. Except for an occasional favorable editorial 16 . 22 and some general acknowledgment that thromboangiitis obliterans had been overdiagnosed in the past, it must be admitted that all respondents found our position unacceptable. In fact, aside from the editorials mentioned above, no further support of our recommendation From the Department of Medicine. The Jewish Hospital of St. Louis and The Washington University School of Medicine "John E. and Adaline Simon Professor of Medicine, Washington University School of Medicine, and Physician-in-Chief, The Jewish Hospital of St. Louis, St. Louis, Missouri This work was supported in part by the Sig and Clara Wolfort Research Fund.
Surgical Clinics of North America- Vol. 49, No.3, June, 1969
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concerning thromboangiitis obliterans has appeared in print during the past decade. Testimony in favor of retaining thromboangiitis obliterans as a distinct entity has been published in the form of letters, editorials, and reviews by internists, surgeons, and pathologists from this country and abroad. Many of the statements reiterate previous observations to the effect that thromboangiitis obliterans is recognizable as a specific entity." One essayist made his comments almost immune to rebuttal by the charm and wit of his poetic introduction to an editorial entitled "Buerger's Disease Retrieved."34 Another vascular specialist summarized his views as follows: "In conclusion, it appears to serious workers in the field of peripheral vascular disease that the fantastic attempt of a small group with undocumented evidence to completely discredit the monumental work of a number of careful scientists of international fame is to be condemned."63 Other serious workers, happily, have approached the specificity of Buerger's disease as a distinct entity in terms of bringing new evidence to bear on this disease. t Before examining the substance of these reports, it is appropriate to restate Leo Buerger's own description of the entity that bears his name, for in his various publications, Buerger described in great detail the characteristics of thromboangiitis obliterans.! According to Buerger, thromboangiitis obliterans is a specific, idiopathic, recurrent, segmental, inflammatory, obliterative vascular disease involving principally the medium-sized arteries and veins of the extremities and only rarely the visceral vessels. The clinical picture is dominated by symptoms and signs referable to recurrent progressive peripheral arterial insufficiency. The lower extremities are involved more frequently than the arms, and ischemi~ often terminates in gangrene. The disease is particularly common in young Jewish male smokers, superficial and deep phlebitis is frequent, and roentgenologic evidence of peripheral arterial calcification is usually absent. Special arterial and venous lesions are described and separated into three stages. The first, or acute, stage is characterized by an acute inflammation involving all coats of the vessel wall, together with occlusive thrombosis. Within the thrombus, there are first purulent and later giant cell foci, both of which disappear when organization begins. The second, or intermediate, stage is one of healing. In the third stage, the intima is thickened and the lumen occluded by connective tissue. The inflammatory cells have disappeared and fibrous tissue has formed in the adventitia, binding together artery, veins, and nerve. In all three stages, the vessel wall is normal subjacent to the occluding thrombus. These findings distinguish the vascular disease of thromboangiitis obliterans from atherosclerosis and from arteritis in which damage to the internal elastic lamina can be demonstrated. In his various reports, Buerger describes in great detail the characteristics of thromboangiitis obliterans. He carefully differentiates it ':'Seereferences 1,2,4,17,20,21,33,34,41,44,48,55,56,58,59,63,65, 66, 69,78, and 85. tSee references 18, 27, 36,37,49,50,51,52,61,64, and 72. !See references 8, 9, 10, 11, 12, 13, 14, and 15.
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from Raynaud's disease, erythromelalgia, sclerodactylia, atherosclerosis, intimal inflammation, and diffuse vasculitis. He also notes that the small arteries and capillaries are free of disease, that "skip" areas in which the vessel is normal are common, and that the amount of perivascular reaction even in different areas of the same vessel is extremely variable. In view of present knowledge of the relative frequency of atherosclerosis among young men, it is no longer reasonable to consider age and sex as distinguishing features of Buerger's disease. To appreciate how this association may initially have come about, it is necessary to recall that Buerger's original investigations were completed in an era when neither the frequency of clinically significant atherosclerosis nor the ubiquity of thromboembolism was fully recognized. Herrick's publication concerning the correlation of the pathology of coronary occlusion with the clinical picture of myocardial infarction, for example, was published 4 years after Buerger described the disease that bears his name. 32 Buerger's initial studies also preceded by several decades the extensive observations on the high incidence of coronary atherosclerosis in young men.24. 86 It is now clear that the secondary and tertiary lesions of thromboangiitis obliterans are nonspecific and could result from arterial obstruction of any cause and that the extent of perivascular fibrosis is no greater in thromboangiitis obliterans than in other thrombotic disorders.6. 26. 47. 74. 82 Moreover, despite the passage of more than half a century, the etiology and pathogenesis of Buerger's disease remains obscure. 7. 23. 38. 73. 76 Recent attempts to relate the disease to abnormalities in coagulation18 or to a genetic basis 27 have been unsuccessful. At present, validation of thromboangiitis obliterans as an entity appears to rest pathologically upon the specificity of the acute histologic lesions, radiographically upon the unique features of peripheral arteriography, and clinically on the response to therapy and the recognition of a constellation of signs and symptoms that have been termed the Buerger syndrome. 50
HISTOLOGY OF FIRST STAGE LESION The acute vascular lesion has occasionally been described in superficial veins but only rarely in deep veins or in arteries. The paucity of such acute lesions in the deep vessels has usually been attributed to the fact that the affected limbs are amputated in the late stages of the disease. However, if the natural history of Buerger's disease is indeed that of an episodic, recurrent, and relapsing process, it is remarkable that the traces of the acute lesion are seen so rarely in these specimens. This is particularly significant in view of the fact that recent arterial thrombi devoid of acute inflammatory reaction have often been noted in such amputated extremities. Bland venous thrombosis with little or no cellular reaction was frequently seen by Buerger in addition to the characteristic acute lesions. He did not indicate the relative frequency of these two distinct mor-
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phologic processes and apparently considered both to be significant. In all the material available to him from amputated limbs, however, the typical acute lesion was noted in the deep vessels of only three extremities. Because of this paucity of deep venous lesions, Buerger, in his later writings, relied on the findings in the superficial veins for evidence of the acute specific lesion. Although these superficial venous lesions were also uncommon ("many of our biopsies were disappointing"),t2 he nevertheless considered them "specific," "absolutely typical and diagnostic," and "an initial manifestation of the pathology of the disease, thromboangiitis obliterans."1l In 1939, he stated that in the absence of evidence of this acute stage the diagnosis should not be made. 13 Difficulties arise when one attempts to document the acute lesion in published photomicrographs. Although a few photographs of such lesions 30 . 38. 46. 53 resemble in part the picture described by Buerger, it is often difficult to determine whether the vessel is an artery or a vein, whether the vessel wall is intact, whether the surrounding area is free of infection, or even whether a septic endocarditis may have been present. Evidence has been produced since 1960 showing giant cells within arterial thrombP' 27. 37. 51, 55 Some of these specimens show disruption of the arterial wall, especially the internal elastic lamina, suggesting an arteritis distinct from the pathology described by Buerger. Other specimens'~ demonstrate a histologic picture properly identifiable as a Buerger's lesion. 51 No questions have been raised concerning the recognition of the venous lesion. Similarly, the existence of the acute arterial lesion can no longer be disputed. Fortunately, the issue of the identity of thromboangiitis obliterans does not, in the final analysis, turn on the inconclusive evidence of whether an acute arterial or venous lesion has been seen. It rests, rather, on the specificity of this lesion. From the pathologic point of view, however, specificity is based upon such features as inflammation without necrosis and the presence of giant cells within the thrombus. Acute venous or arterial thrombosis is usually associated with little or no inflammatory reaction in the vessel wall, and this was true in most vein biopsies reported by Buerger. Doubts have been expressed about the specificity of the venous lesion. 35 . 47. 60 As shown in our previously published data on venous biopsies, however, the degree of reactive inflammation even in an hemorrhoidal vein may vary greatly and may occasionally be as marked as that observed by Buerger. 82 The specificity of the lesion cannot rest on the presence of giant cells alone, since these vary from specimen to specimen, from one section to another in a single specimen, may be entirely absent from some areas, and can, moreover, be found occasionally in recent organizing thrombi obtained from patients devoid of peripheral arterial or venous disease. Buerger himself
*1 am indebted to Dr. Victor McKusick and his associates at the Johns Hopkins Hospital and Medical School for the opportunity to review the microscopic slides of some of the typical acute arterial lesions found in their study.
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stated at one time that the giant cell was merely one manifestation of early organization,'4 and an eminent pathologist, convinced of the identity of thromboangiitis obliterans, has written, "There is so much variation from case to case, depending on the stage of the disease or the characteristic capriciousness of the lesions, that it is difficult to give a succinct account of the histology."47 Whereas the Sternberg-Reed cell is pathognomonic for the diagnosis of Hodgkin's disease, the relation of the sarcoid lesion to sarcoidosis is not specific and serves to illustrate how difficult it is to find an "absolutely diagnostic" lesion on pathologic grounds alone. To what extent the observed pathology depends on the cellular reactivity of the vessels of young men is unknown. If, in addition, one recognizes that the lesion may be mimicked, wholly or in part, by other less specific processes and that the etiologic agent and the pathogenetic mechanisms remain obscure, then there seems little justification for permitting the whole case for thromboangiitis obliterans to rest entirely on this lesion.
TOBACCO The existence of an intimate relation between smoking and Buerger's disease has, with good reason, received widespread acceptance. On the one hand, there are claims that tobacco is the cause of thromboangiitis obliterans ,'7 whereas the disease has been reported to exist among patients who do not smoke at all. 3. 60 It has been stated that the disease is uniformly progressive in all patients who continue to smoke, whereas the pathologic process is arrested in those who abstain from tobacco. 64 . 67 This one-to-one relationship between smoking and disease progression has been disputed.'8, 82 Since smoking is now as common among women as among men, some investigators have asked why thromboangiitis obliterans is still very rare in women.' Moreover, several investigators, convinced that the progression of Buerger's disease is related to smoking, have nevertheless recommended specific therapy beyond cessation of smoking.'7, 48, 58, 68, 80 Finally, there are the observations that abstinence from tobacco has been found beneficial in peripheral arterial insufficiency from any cause. In one study, 99 patients with atherosclerosis and 54 patients with thromboangiitis obliterans were subjected to the same therapeutic regimen consisting of the avoidance of tobacco, cold, trauma, and undue exertion. 5 The improvement in both groups of patients was similar. In another study, the smoking habits of 400 patients in a peripheral vascular clinic were reviewed. All but two of these patients were smokers. Uniform improvement was observed among all patients who discontinued use of tobacco. 57 An increased incidence of cutaneous sensitivity to tobacco in subjects with Buerger's disease has been both claimed31, 70 and denied. 79 ,83 No consistent difference in skin temperature, blood pressure, or pulse response to smoking has been found among persons who showed skin sensitivity to tobacco as compared to those who did not. 45 The experimental and clinical evidence shows that the smoking of tobacco is probably only a contributory factor and not an etiologic one and peripheral
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vascular constriction occurs after the use of tobacco regardless of the primary pathologic condition in the vessels of the affected extremity.62 There is, in short, no evidence from a suitably controlled study to indicate that tobacco is more harmful to patients said to have Buerger's disease than to patients of similar age and with similar degrees of arterial obstruction from other causes.
ARTERIOGRAPHY In recent years, arteriography has come into vogue as a means by which Buerger's disease can be diagnosed. 50. 51. 71. 72 McKusick studied 20 femoral and 18 brachial arteriograms from 12 patients with the diagnosis of Buerger's syndrome and compared the angiographic data with that obtained in three patients with the diagnosis of systemic arterial embolism and five patients with atherosclerotic peripheral vascular disease. 5o "Corkscrew" collaterals and a "rippling" or corrugated appearance of arteries resembling the neck of a gooseneck lamp were observed. These findings were unique and distinctive enough to constitute an important reason for considering Buerger's disease an entity. Szilagyi also noted this corrugation and stated that "whatever diagnostic uncertainty remained in a case after the evaluation of the clinical findings, it was almost invariably dispelled by the results of the angiographic examination - this is a most intriguing lesion since it may be specific to thromboangiitis obliterans-the only finding for which such a claim can be made."72 This interpretation, however, has not been confirmed by others. DeBakey noted "corkscrew collateral channels" in patients with diabetes mellitus and peripheral vascular insufficiency as well as in patients with a diagnosis of Buerger's disease. 19 Theander demonstrated stationary arterial waves, "a string of pearls effect," in young patients with acute arterial embolism. 75 Wickbom noted "small circular constrictions" in vessels in which a catheter and metal guide were inserted and noted their disappearance after injection of Priscoline. B4 He found these constrictions in patients with Raynaud's phenomenon, tumor, and atherosclerosis, as well as in patients with Buerger's disease. Lindbom, after noting spasm in arteriograms and in some instances many short circular constrictions, concluded that "the arterial wall should be judged arteriographically with great caution in cases in which a catheter or another object is or has been present in the lumen and in which the vessel is suddenly dilated by forceful injection."42 More recently, Kohler has stated that it is difficult to find a physical explanation for the arteriographically demonstrated regular, alternating changes in arterial width. The most likely cause of the changes is spastic circular constrictions in the vessel. wall induced by irritation from the contrast medium in subjects with especially sensitive vessels. Although Kohler believes that very slight constrictions may be difficult to distinguish from diffuse intimal thickenings, the appearance causes no problems in differential diagnosis in typical cases. 39 Dr. Noah Susman of the Radiology Department of the Jewish Hospital of St. Louis has recently reviewed a small number of unselected
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arteriograms of the lower limbs and observed the "rippling" phenomena in roentgenograms of five patients. Two were young men with atherosclerosis of the aortoiliac area with rippling of the superficial femoral arteries. One was a young woman who had a femoral arteriogram to delineate the blood supply of a calf tumor; another was a young man in whom arteriography was performed to demonstrate a traumatic injury to the popliteal artery. Rippling of the femoral artery was observed in both patients. The fifth patient was a young man who presented with a chief complaint of leg cramps at rest and who exhibited good peripheral pulses: his arteriogram showed rippling but no obstruction of the femoral artery. It would appear therefore that the rippling effect described by McKusick is not unique to patients with Buerger's disease and that the uncertainty of Szilagyi in the diagnosis of thromboangiitis obliterans is not dispelled by its presence.
BUERGER'S SYNDROME It is now widely agreed that in the past the term Buerger's disease was loosely applied to young men with peripheral arterial insufficiency from diverse causes. The vast majority developed their symptoms and signs secondary to peripheral atherosclerosis. There were also a few young men mislabeled as having thromboangiitis obliterans who developed their ischemia secondary to endocardial mural thrombi and still another group in whom the ischemia resulted from an arteritis distinct from that described by Buerger. Evidence previously presented by us has clearly demonstrated that Buerger himself only rarely found proof that the patients he studied had thromboangiitis obliterans,82 an observation that should put to rest the claim that Buerger's disease was a more common entity before 1930 than it was after that date. The argument for the existence of Buerger's disease as an entity is, in fact, reduced to a constellation of clinical findings noted by many observers 27 • 33. 64 and effectively characterized as the Buerger syndrome by McKusick: "Regardless of whether one accepts Buerger's disease as an entity, one cannot question the existence of a clinical syndrome which can with historic justice be termed the Buerger syndrome: occlusive peripheral vascular disease, that occurs almost exclusively in men. It begins before 35 years in most, and before 20 years in some. In many, it affects the arms as well as the legs; it occurs almost solely in tobacco smokers; it demonstrates an intimate relationship of remission and relapse to cessation or resumption of smoking; and it manifests excruciating pain out of proportion to that found in other forms of peripheral vascular disease. In many, it is associated with migratory thrombophlebitis, but it is not associated with diabetes mellitus, hypercholesterolemia, or heart disease, which might be the source of emboli."51 There are few physicians who have not seen patients fitting this description. But how specific are these findings? Silbert, in spite of the fact that he reported on perhaps the largest clinical series of patients with Buerger's disease, denied the existence of any pathognomonic clinical finding and stated that the diagnosis could only be made after
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other causes of arterial insufficiency had been excluded. 67 Moreover, when causes of arterial obstruction other than thrombosis are excluded, in what way are those rare cases labeled Buerger's syndrome distinguished from other patients with thrombosis to whom the eponym has not been applied?
RECONCILIATION When the investigators at the Boston Beth Israel Hospital concluded the disease originally described by Buerger is indistinguishable from atherosclerosis, systemic emboli, or peripheral arterial or venous thrombosis, singly or in combination,82 McKusick took exception to this allinclusive phraseology. He observed that "since all occlusive vascular disease is, in the last analysis, thrombosis, the latter part of the statement is difficult to refute."51 So, indeed, it is. Therein lies a resolution to the recent controversy concerning the identity of thromboangiitis obliterans. These uncommon patients, who fit the Buerger syndrome, can be considered to have idiopathic peripheral arterial thrombosis, possibly on the basis of systemic hypercoagulability or secondary to some immunologic disorder, as suggested by others in the past. 29 • 40. 43.77. 81 Idiopathic arterial thrombosis differs from its counterpart in the veins largely by its relative rarity, a difference accounted for in part by the comparative ease with which venous flow may be retarded. My original demurrer was to accepting what Buerger described as a specific disease. My current reservation toward the term Buerger's syndrome is that it potentially subdivides an already idiopathic group and does not thereby clarify whether the terms Buerger's syndrome and idiopathic peripheral arterial thrombosis are synonyms or describe different entities. If they are the former, then the advantages of the term are not clear; if the latter is true, then one must ask what the syndromes that describe the remaining patients with arterial thrombotic disease are. My personal conjecture is that the term Buerger's syndrome is presently being used as an umbrella for the occasional patient with peripheral arterial thrombosis the cause of which is unknown. The semantics of this terminology will not, of course, be settled by debate. For after all the substantive issue concerns the factors initiating arterial thrombosis, not the label of the consequence of the obstructionso long as the label does not obscure the nature or the management of the underlying biologic problem. If this reasoning is valid, can there be any advantage in discarding the term Buerger syndrome, which memorializes an investigator whose stimulus to the study of the peripheral circulation was unique? One rather practical concern presents itself, namely, that we may protect patients from treatments still recommended for the therapy of Buerger's disease that are not suggested for patients with arterial insufficiency from other causes. Even though intravenous injections of saline and diets free of rye bread are no longer prescribed, the therapeutic armamentarium still includes malarial therapY,17 bilateral adrenalectomy,58. 80 hyperbaric oxygen,48 tolbutamide,68 phenylbutazone and prednisone. 54
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As for the claim that patients with Buerger's disease have a better prognosis than those with peripheral atherosclerosis,52 would not the patient with idiopathic peripheral arterial thrombosis also have a better outlook than the individual with ischemia secondary to atherosclerosis?
REFERENCES 1. Abramson, D. I.: Diagnosis and treatment of thromboangiitis obliterans. Geriatrics, 20:28, 1965. 2. Abramson, D. 1., Zayas, A. M., Canning, J. R, and Edinburg, J. J.: Thromboangiitis obliterans: A true clinical entity. Amer. J. Cardiol., 12:107, 1963. 3. Allen, E. V., and Brown, G. E.: Thromboangiitis obliterans: Clinical study of 200 cases: Etiology, pathology, symptoms, diagnosis. Ann. Int. Med., 1 :535, 1928. 4. Barker, N. W.: The case for retention of the diagnostic category "thromboangiitis obliterans." Circulation, 25: 1, 1962. 5. Bernheim, A. R, and London, 1. M.: Arteriosclerosis and thromboangiitis obliterans: Report of cases and treatment. J.A.M.A., 108:2102, 1937. 6. Boyd, A. M., Ratcliffe, A. H., Jepson, R P., and James, G. W. H.: Intermittent claudication: Clinical study. J. Bone Joint Surg., 31B:325, 1949. 7. Brown, G. E., and Allen, E. V.: Thromboangiitis obliterans: Clinical, physiologic and pathologic studies: Collaborating in pathology, with Howard R Mahomer. Philadelphia, W. B. Saunders Company, 1928. 8. Buerger, L.: Association of migrating thrombophlebitis with thromboangiitis obliterans. Internat. Clin., s. 193:84, 1909. 9. Buerger, L.: Concerning vasomotor and trophic disturbance of upper extremities, with particular reference to thromboangiitis obliterans. Amer. J. Med. Sc., 149:210, 1915. 10. Buerger, L.: Pathology of thromboangiitis obliterans. Med. Rec., 97:431, 1920. 11. Buerger, L.: Recent studies in pathology of thromboangiitis obliterans. J. Med. Res., 31 :181,1914-1915. 12. Buerger, L.: The circulatory disturbances of the extremities: Including gangrene, vasomotor and trophiC disorders. Philadelphia, W. B. Saunders Company, 1924. 13. Buerger, L.: Thromboangiitis obliterans: Concepts of pathogenesis and pathology. J. Internat. Chir., 4:399, 1939. 14. Buerger, L.: Veins in thromboangiitis obliterans, with particular reference to arteriovenous anastomosis as cure for condition. J.A.M.A., 52: 1319, 1909. 15. Buerger, L., and Kalinski, D. J.: Complement-fixation tests in thromboangiitis obliterans. Med. Rec., 78:665, 1910. 16. Buerger's disease. (Editorial.) Brit. Med. J., 2: 1214, 1960. 17. Corelli, F.: Buerger's disease. (Letter.) Brit. Med. J., 1 :209, 1961. 18. Craven, J. L., and Cotton, R C.: Haematological differences between thromboangiitis obliterans and atherosclerosis. Brit. J. Surg., 54:862, 1967. 19. DeBakey, M. E., Crawford, E. S., Garrett, H. E., Cooley, D. A., Morris, G. C., and Abbott, J. P.: Occlusive disease of the lower extremities in patients 16 to 37 years of age. Ann. Surg., 159:873, 1964. 20. DeTakats, G.: Classification of Buerger's disease. (Letter.) New Eng. J. Med., 263:412, 1960. 21. Dible, J. H.: Does Buerger's disease exist? (Letter.) Lancet, 2: 1138, 1960. 22. Does Buerger's disease exist? (Editorial.) Lancet, 2:969, 1960. 23. Diirch-Miinchen, H.: Die sogenannte "Thrombangiitis obliterans" im Rahmen der infektios-toxischen Gefassentzundungen. Verhandl. d. deutsch. path. Gesellsch., 25: 272, 1930. 24. Enos, W. F., Holmes, R H., and Beyer, J.: Coronary disease among United States soldiers killed in action in Korea: Preliminary report. J.A.M.A., 152:1090, 1953. 25. Fisher, C. M.: Cerebral thromboangiitis. Medicine, 36:169,1957. 26. Gery, L., Fontaine, R, and Branzeu, P.: Les lesions chroniques obliterantes des arteresdes membres: (estude anatomo-clinique). J. Internat. Chir., 4:427, 1939. 27. Goodman, R M., Elian, B., Mozes, M., and Deutsch, V.: Buerger's disease in Israel. Amer. J. Med., 39:601, 1965. 28. Gore, 1., and Burrows, S.: Reconsideration of pathogenesis of Buerger's disease. Amer. J. Clin. Path., 29:319, 1958. 29. Gruber, G. B.: Endarteritis obliterans und Kiiltebrand. Beitr. z. path. Anat. u. z. allg. Path., 84:155, 1930. 30. Hall, E. M.: Blood and lymphatic vessels. In Anderson, W. A. D. (ed.): Pathology. 3rd edition. St. Louis, C. V. Mosby Co., 1957, p. 521. 31. Harkavy, J.: Tobacco sensitiveness in thromboangiitis obliterans, migrating phlebitis and coronary artery disease. Bull. N.Y. Acad. Med., 9:318, 1933.
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32. Herrick, J. B.: Clinical features of sudden obstruction of coronary arteries. J.A.M.A., 59:2015, 1912. 33. Hershey, F. B., Pareira, M. D., and Ahlvin, R C.: Quadrilateral peripheral vascular disease in the young adult. Circulation, 26:1261,1962. 34. Horowitz, 0.: Buerger's disease retrieved. (Editorial.) Ann. Int. Med., 55:341, 1961. 35. Horton, B. J., and Brown, G. E.: Thromboangiitis obliterans among women. Arch. Int. Med., 50:884, 1932. 36. Inada, K, Hayaski, M., and Okatani, T.: Chronic occlusive arterial disease of lower extremity in Japan. Arch. Surg., 88:454, 1964. 37. Ishikawa, K, Kawase, S., and Mishima, Y.: Occlusive arterial disease in extremities with special reference to Buerger's disease. Angiology, 13:398, 1962. 38. Jager, E.: Zur pathologischen Anatomie der Thromboangiitis obliterans bei juveniler Extremitatengangriin. Virchows Arch. f. path. Anat., 284:526, 584, 1932. 39. Kohler, R: Regular alternating changes in arterial width in lower limb angiograms. Acta Radiologica Diag., 3:529, 1963. 40. Kulka, J. P.: Histopathologic studies in frostbite rabbit: In Ferrer, M. 1. (ed.): Transactions of the Fourth Conference on Cold Injury, November 7-9,1955, Princeton, New Jersey. New York, Josiah Macy, Jr., Foundation, 1957, p. 97. 41. Lewes, D.: Does Buerger's disease exist? (Letter.) Lancet, 1: 170, 1961. 42. Lindbom, A: Arterial spasm caused by puncture and catheterization. Acta Radiologica, 47:449, 1957. 43. Livingston, W. K: Skin temperature studies. III. Case report. Thrombosis of arteries of extremities, brain, heart and kidney, with general discussion of vascular disease. West. J. Surg., 41 :21, 1933. 44. Luttwak, E. M., and Eyal, Z.: Thromboangiitis obliterans: The case for Buerger's disease. Israel Med. J., 22:33, 1963. 45. Maddock, W. G., Malcolm, R L., and Coller, F. A.: Thromboangiitis obliterans and tobacco: Influence of sex, race, and skin sensitivity to tobacco on cardiovascular response to smoking. Amer. Heart J., 12:46, 1936. 46. Mallory, T. B.: Acute thromboangiitis obliterans of coronary artery. In Monroe, R T. (ed.): Medical Papers: Dedicated to Henry Ashbury Christian, Physician and Teacher, from His Present and Past Associates and House Officers at the Peter Bent Brigham Hospital, Boston, Massachusettes, in Honor of His Sixtieth Birthday, February 17, 1936. Baltimore, The Waverly Press, 1936, p. 147. 47. Martin, P., Lynn, R B., Dible, J. H., and Aird, I. (eds.): Peripheral Vascular Disorders. Edinburgh, E. & S. Livingstone, 1956. 48. Maudsley, R H., Hopkinson, W. 1., Horne, J., and Williams, K G.: Buerger's disease. Lancet, 2:1245,1964. 49. McKusick, V. A, and Harris, W. S.: Buerger's syndrome in the Orient. (Letter.) Lancet, 1:1117,1961. 50. McKusick, V. A, Harris, W. S., Ottesen, O. E., and Goodman, R M.: The Buerger syndrome in the United States. Arteriographic observations with special reference to involvement of the upper extremities and the differentiation from atherosclerosis and embolism. Bull. Johns Hopkins Hosp., 110:145, 1962. 51. McKusick, V. A., Harris, W. S., Ottesen, O. E., Goodman, R M., Shelley, W. M., and Bloodwell, R D.: Buerger's disease. A distinct clinical and pathologic entity. J.AM.A, 181 :5, 1962. 52. McPherson, J. R, Juergens, J. L., and Gifford, R W.: Thrombophlebitis obliterans and arteriosclerosis obliterans. Clinical and prognostic differences. Ann. Int. Med., 59:288, 1963. 53. Meleney, F. L., and Miller, G. G.: Contribution to study of thromboangiitis obliterans. Ann. Surg., 81 :976, 1925. 54. Monserrat, J.: Tratamiento de Thromboangitis Obliterante con Fenilbutazona y Prednisona. Angiologica, 11 :409, 1959. 55. Montorsi, W., and Ghiringhelli, C.: A case of Buerger's disease in women. Angiology, 12:376, 1961. 56. Oldham, J. B.: Buerger's disease. (Letter.) Brit. Med. J., 1 :503, 1961. 57. Oldham, J. B., and Pemberton, H. S.: Aetiology of vascular disease. Brit. Med. J., 2:628, 1953. 58. Orban, F.: New trends in the treatment of thromboangeiosis (Buerger's disease). Ann. Royal ColI. Surg., 28:69, 1961. 59. Peacock, J.: Buerger's disease. Nursing Times, 58:1545,1962. 60. Perla, D.: Analysis of 41 cases of thromboangiitis obliterans, with report of case involving coronaries and aorta. Surg. Gynec. Obst., 41 :21, 1925. 61. Razdan, A. N., Singh, R P., and Srivastava, V. K: Thromboangiitis obliterans. A clinical study of 125 cases. Int. Surg., 47:122,1967. 62. Roth, G. M.: Tobacco and the cardiovascular system. Springfield, Illinois, Charles C Thomas, 1951, p. 1. 63. Samuels, S.: Buerger's disease. (Editorial.) Angiology,,. 11 :213, 1960.
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64. Schatz, I. G., Fine, G., and Eyler, W. R.: Thromboangiitis obliterans. Brit. Heart J., 28:84, 1966. 65. Short, D. W.: Some aspects of occlusive arterial disease of the upper limbs. Scot. Med. J., 9:319, 1964. 66. Significance of thromboangiitis obliterans. (Editorial.) J.A.M.A., 195:861, 1966. 67. Silbert, S.: Etiology of thromboangiitis obliterans. J.A.M.A., 129:5, 1945. 68. Singh, I., and Brara, N. S.: Tolbutamide in the treatment of thromboangiitis obliterans. Lancet, 2:625, 1960. 69. Snapper, I.: Thromboangiitis obliterans. In Bedside Medicine. New York, Grune and Stratton, 1960, p. 64. 70. Sulzberger, M. B., and Feit, E.: Studies in tobacco hypersensitivity. II. Thromboangiitis obliterans with positive urticarial skin reactions and negative reagin findings. J. Immunol., 24:425,1933. 71. Sutton, D.: Arteriography. Edinburgh, E. & S. Livingstone, 1962, p. 84. 72. Szilagyi, D. E., DeRus so, F. J., and Elliott, J. P.: Thromboangiitis obliterans. Arch. Surg., 88:824, 1964. 73. Telford, E. D., and Stopford, J. S. B.: Thromboangiitis obliterans. Brit. Med. J., 2:1035, 1924. 74. Telford, E. D., and Stopford, J. S. B.: Thromboangiitis obliterans, with special reference to its pathology and results of sympathectomy. Brit. Med. J., 1 :863,1935. 75. Theander, G.: Arteriographic demonstration of stationary arterial waves. Acta RadioIOgica, 53:417,1960. 76. Theis, F. V.: Thromboangiitis obliterans: 30-year study. J. Am. Geriatrics Soc., 6:106, 1958. 77. Theis, F. V., and Freeland, M. R.: Blood in thromboangiitis obliterans. Arch. Surg., 38:191, 1939. 78. Thieme, W. T.: Buerger's disease. Further support of the entity. Northwest Med., 64:264, 1965. 79. Trasoff, A., Blumstein, G., and Marks, M.: Immunologic aspect of tobacco in thromboangiitis obliterans and coronary artery disease. J. Allergy, 7:250, 1.936. 80. Wertheimer, P., and Mounier-Kuhn, A.: A propos de la surrenalectomie bilaterale dans les thromboangioses. Mem. Acad. Chir., 86:529, 1960. 81. Wessler, S., Cohen, S., and Fleischner, F. G.: Temporary thrombotic state: Application of this concept to therapy of recurrent thromboembolism, with bacteriologic and roentgenologic considerations in differential diagnosis of pulmonary infarction and pneumonia. New Eng. J. Med., 254:413,1956. 82. Wessler, S., Ming, S. C., Gurewich, V., and Freiman, D. G.: A critical eyaluation of thromboangiitis obliterans. The case against Buerger's disease. New Eng. J. Med., 262:1149, 1960. 83. Westcott, F. H., and Wright, I. S.: Tobacco allergy and thromboangiitis obliterans. J. Allergy, 9:555, 1937-1938. 84. Wickbom, I., and Bartley, 0.: Arterial spasm in peripheral arteriography. Using the catheter method. Acta Radiologica, 47:433, 1957. 85. Wright, I. S.: The treatment of occlusive arterial disease, viewpoint of an internist. J.A.M.A., 183:186, 1963. 86. Yater, W. M., Traum, A. H., Brown, W. G., Fitzgerald, R. P., Geisler, M. A., and Wilcox, B. B.: Coronary artery disease in men 18 to 39 years of age: Report of 866 cases, 450 with necropsy examinations. Amer. Heart J., 36:334, 481, 683, 1948. 216 South Kingshighway St. Louis, Missouri 63110
Thromboangiitis obliterans was originally described by Leo Buerger in 1908 and became firmly established along with atherosclerosis as one of the two major causes of peripheral arterial occlusive disease. Beginning in 1933, skepticism concerning the identity of thromboangiitis obliterans was expressed by several investigators. 25 . 26. 28. 43 An analysis of the entire experience with Buerger's disease at the Beth Israel Hospital in Boston from 1929 to 1956 was published in 1960, together with a review of the various considerations in the literature that had perpetuated thromboangiitis obliterans as an entity.82 It was concluded from this study that the disease originally described by Buerger was indistinguishable from atherosclerosis, systemic embolization, or peripheral arterial or venous thrombosis, singly or in combination. Because of the difficulties inherent in establishing a negative hypothesis, any attempt to prove that thromboangiitis obliterans did not then and does not now exist, can approach such a goal only asymptotically. Nevertheless, in 1960, the available evidence appeared to favor the view that Buerger's disease had never been and was not then an entity in either the clinical or the pathologic sense and that the term should be discarded. 82 The response to this recommendation was not large, but what did appear in print was vigorous. Except for an occasional favorable editorial 16 . 22 and some general acknowledgment that thromboangiitis obliterans had been overdiagnosed in the past, it must be admitted that all respondents found our position unacceptable. In fact, aside from the editorials mentioned above, no further support of our recommendation From the Department of Medicine. The Jewish Hospital of St. Louis and The Washington University School of Medicine "John E. and Adaline Simon Professor of Medicine, Washington University School of Medicine, and Physician-in-Chief, The Jewish Hospital of St. Louis, St. Louis, Missouri This work was supported in part by the Sig and Clara Wolfort Research Fund.
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concerning thromboangiitis obliterans has appeared in print during the past decade. Testimony in favor of retaining thromboangiitis obliterans as a distinct entity has been published in the form of letters, editorials, and reviews by internists, surgeons, and pathologists from this country and abroad. Many of the statements reiterate previous observations to the effect that thromboangiitis obliterans is recognizable as a specific entity." One essayist made his comments almost immune to rebuttal by the charm and wit of his poetic introduction to an editorial entitled "Buerger's Disease Retrieved."34 Another vascular specialist summarized his views as follows: "In conclusion, it appears to serious workers in the field of peripheral vascular disease that the fantastic attempt of a small group with undocumented evidence to completely discredit the monumental work of a number of careful scientists of international fame is to be condemned."63 Other serious workers, happily, have approached the specificity of Buerger's disease as a distinct entity in terms of bringing new evidence to bear on this disease. t Before examining the substance of these reports, it is appropriate to restate Leo Buerger's own description of the entity that bears his name, for in his various publications, Buerger described in great detail the characteristics of thromboangiitis obliterans.! According to Buerger, thromboangiitis obliterans is a specific, idiopathic, recurrent, segmental, inflammatory, obliterative vascular disease involving principally the medium-sized arteries and veins of the extremities and only rarely the visceral vessels. The clinical picture is dominated by symptoms and signs referable to recurrent progressive peripheral arterial insufficiency. The lower extremities are involved more frequently than the arms, and ischemi~ often terminates in gangrene. The disease is particularly common in young Jewish male smokers, superficial and deep phlebitis is frequent, and roentgenologic evidence of peripheral arterial calcification is usually absent. Special arterial and venous lesions are described and separated into three stages. The first, or acute, stage is characterized by an acute inflammation involving all coats of the vessel wall, together with occlusive thrombosis. Within the thrombus, there are first purulent and later giant cell foci, both of which disappear when organization begins. The second, or intermediate, stage is one of healing. In the third stage, the intima is thickened and the lumen occluded by connective tissue. The inflammatory cells have disappeared and fibrous tissue has formed in the adventitia, binding together artery, veins, and nerve. In all three stages, the vessel wall is normal subjacent to the occluding thrombus. These findings distinguish the vascular disease of thromboangiitis obliterans from atherosclerosis and from arteritis in which damage to the internal elastic lamina can be demonstrated. In his various reports, Buerger describes in great detail the characteristics of thromboangiitis obliterans. He carefully differentiates it ':'Seereferences 1,2,4,17,20,21,33,34,41,44,48,55,56,58,59,63,65, 66, 69,78, and 85. tSee references 18, 27, 36,37,49,50,51,52,61,64, and 72. !See references 8, 9, 10, 11, 12, 13, 14, and 15.
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from Raynaud's disease, erythromelalgia, sclerodactylia, atherosclerosis, intimal inflammation, and diffuse vasculitis. He also notes that the small arteries and capillaries are free of disease, that "skip" areas in which the vessel is normal are common, and that the amount of perivascular reaction even in different areas of the same vessel is extremely variable. In view of present knowledge of the relative frequency of atherosclerosis among young men, it is no longer reasonable to consider age and sex as distinguishing features of Buerger's disease. To appreciate how this association may initially have come about, it is necessary to recall that Buerger's original investigations were completed in an era when neither the frequency of clinically significant atherosclerosis nor the ubiquity of thromboembolism was fully recognized. Herrick's publication concerning the correlation of the pathology of coronary occlusion with the clinical picture of myocardial infarction, for example, was published 4 years after Buerger described the disease that bears his name. 32 Buerger's initial studies also preceded by several decades the extensive observations on the high incidence of coronary atherosclerosis in young men.24. 86 It is now clear that the secondary and tertiary lesions of thromboangiitis obliterans are nonspecific and could result from arterial obstruction of any cause and that the extent of perivascular fibrosis is no greater in thromboangiitis obliterans than in other thrombotic disorders.6. 26. 47. 74. 82 Moreover, despite the passage of more than half a century, the etiology and pathogenesis of Buerger's disease remains obscure. 7. 23. 38. 73. 76 Recent attempts to relate the disease to abnormalities in coagulation18 or to a genetic basis 27 have been unsuccessful. At present, validation of thromboangiitis obliterans as an entity appears to rest pathologically upon the specificity of the acute histologic lesions, radiographically upon the unique features of peripheral arteriography, and clinically on the response to therapy and the recognition of a constellation of signs and symptoms that have been termed the Buerger syndrome. 50
HISTOLOGY OF FIRST STAGE LESION The acute vascular lesion has occasionally been described in superficial veins but only rarely in deep veins or in arteries. The paucity of such acute lesions in the deep vessels has usually been attributed to the fact that the affected limbs are amputated in the late stages of the disease. However, if the natural history of Buerger's disease is indeed that of an episodic, recurrent, and relapsing process, it is remarkable that the traces of the acute lesion are seen so rarely in these specimens. This is particularly significant in view of the fact that recent arterial thrombi devoid of acute inflammatory reaction have often been noted in such amputated extremities. Bland venous thrombosis with little or no cellular reaction was frequently seen by Buerger in addition to the characteristic acute lesions. He did not indicate the relative frequency of these two distinct mor-
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phologic processes and apparently considered both to be significant. In all the material available to him from amputated limbs, however, the typical acute lesion was noted in the deep vessels of only three extremities. Because of this paucity of deep venous lesions, Buerger, in his later writings, relied on the findings in the superficial veins for evidence of the acute specific lesion. Although these superficial venous lesions were also uncommon ("many of our biopsies were disappointing"),t2 he nevertheless considered them "specific," "absolutely typical and diagnostic," and "an initial manifestation of the pathology of the disease, thromboangiitis obliterans."1l In 1939, he stated that in the absence of evidence of this acute stage the diagnosis should not be made. 13 Difficulties arise when one attempts to document the acute lesion in published photomicrographs. Although a few photographs of such lesions 30 . 38. 46. 53 resemble in part the picture described by Buerger, it is often difficult to determine whether the vessel is an artery or a vein, whether the vessel wall is intact, whether the surrounding area is free of infection, or even whether a septic endocarditis may have been present. Evidence has been produced since 1960 showing giant cells within arterial thrombP' 27. 37. 51, 55 Some of these specimens show disruption of the arterial wall, especially the internal elastic lamina, suggesting an arteritis distinct from the pathology described by Buerger. Other specimens'~ demonstrate a histologic picture properly identifiable as a Buerger's lesion. 51 No questions have been raised concerning the recognition of the venous lesion. Similarly, the existence of the acute arterial lesion can no longer be disputed. Fortunately, the issue of the identity of thromboangiitis obliterans does not, in the final analysis, turn on the inconclusive evidence of whether an acute arterial or venous lesion has been seen. It rests, rather, on the specificity of this lesion. From the pathologic point of view, however, specificity is based upon such features as inflammation without necrosis and the presence of giant cells within the thrombus. Acute venous or arterial thrombosis is usually associated with little or no inflammatory reaction in the vessel wall, and this was true in most vein biopsies reported by Buerger. Doubts have been expressed about the specificity of the venous lesion. 35 . 47. 60 As shown in our previously published data on venous biopsies, however, the degree of reactive inflammation even in an hemorrhoidal vein may vary greatly and may occasionally be as marked as that observed by Buerger. 82 The specificity of the lesion cannot rest on the presence of giant cells alone, since these vary from specimen to specimen, from one section to another in a single specimen, may be entirely absent from some areas, and can, moreover, be found occasionally in recent organizing thrombi obtained from patients devoid of peripheral arterial or venous disease. Buerger himself
*1 am indebted to Dr. Victor McKusick and his associates at the Johns Hopkins Hospital and Medical School for the opportunity to review the microscopic slides of some of the typical acute arterial lesions found in their study.
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stated at one time that the giant cell was merely one manifestation of early organization,'4 and an eminent pathologist, convinced of the identity of thromboangiitis obliterans, has written, "There is so much variation from case to case, depending on the stage of the disease or the characteristic capriciousness of the lesions, that it is difficult to give a succinct account of the histology."47 Whereas the Sternberg-Reed cell is pathognomonic for the diagnosis of Hodgkin's disease, the relation of the sarcoid lesion to sarcoidosis is not specific and serves to illustrate how difficult it is to find an "absolutely diagnostic" lesion on pathologic grounds alone. To what extent the observed pathology depends on the cellular reactivity of the vessels of young men is unknown. If, in addition, one recognizes that the lesion may be mimicked, wholly or in part, by other less specific processes and that the etiologic agent and the pathogenetic mechanisms remain obscure, then there seems little justification for permitting the whole case for thromboangiitis obliterans to rest entirely on this lesion.
TOBACCO The existence of an intimate relation between smoking and Buerger's disease has, with good reason, received widespread acceptance. On the one hand, there are claims that tobacco is the cause of thromboangiitis obliterans ,'7 whereas the disease has been reported to exist among patients who do not smoke at all. 3. 60 It has been stated that the disease is uniformly progressive in all patients who continue to smoke, whereas the pathologic process is arrested in those who abstain from tobacco. 64 . 67 This one-to-one relationship between smoking and disease progression has been disputed.'8, 82 Since smoking is now as common among women as among men, some investigators have asked why thromboangiitis obliterans is still very rare in women.' Moreover, several investigators, convinced that the progression of Buerger's disease is related to smoking, have nevertheless recommended specific therapy beyond cessation of smoking.'7, 48, 58, 68, 80 Finally, there are the observations that abstinence from tobacco has been found beneficial in peripheral arterial insufficiency from any cause. In one study, 99 patients with atherosclerosis and 54 patients with thromboangiitis obliterans were subjected to the same therapeutic regimen consisting of the avoidance of tobacco, cold, trauma, and undue exertion. 5 The improvement in both groups of patients was similar. In another study, the smoking habits of 400 patients in a peripheral vascular clinic were reviewed. All but two of these patients were smokers. Uniform improvement was observed among all patients who discontinued use of tobacco. 57 An increased incidence of cutaneous sensitivity to tobacco in subjects with Buerger's disease has been both claimed31, 70 and denied. 79 ,83 No consistent difference in skin temperature, blood pressure, or pulse response to smoking has been found among persons who showed skin sensitivity to tobacco as compared to those who did not. 45 The experimental and clinical evidence shows that the smoking of tobacco is probably only a contributory factor and not an etiologic one and peripheral
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vascular constriction occurs after the use of tobacco regardless of the primary pathologic condition in the vessels of the affected extremity.62 There is, in short, no evidence from a suitably controlled study to indicate that tobacco is more harmful to patients said to have Buerger's disease than to patients of similar age and with similar degrees of arterial obstruction from other causes.
ARTERIOGRAPHY In recent years, arteriography has come into vogue as a means by which Buerger's disease can be diagnosed. 50. 51. 71. 72 McKusick studied 20 femoral and 18 brachial arteriograms from 12 patients with the diagnosis of Buerger's syndrome and compared the angiographic data with that obtained in three patients with the diagnosis of systemic arterial embolism and five patients with atherosclerotic peripheral vascular disease. 5o "Corkscrew" collaterals and a "rippling" or corrugated appearance of arteries resembling the neck of a gooseneck lamp were observed. These findings were unique and distinctive enough to constitute an important reason for considering Buerger's disease an entity. Szilagyi also noted this corrugation and stated that "whatever diagnostic uncertainty remained in a case after the evaluation of the clinical findings, it was almost invariably dispelled by the results of the angiographic examination - this is a most intriguing lesion since it may be specific to thromboangiitis obliterans-the only finding for which such a claim can be made."72 This interpretation, however, has not been confirmed by others. DeBakey noted "corkscrew collateral channels" in patients with diabetes mellitus and peripheral vascular insufficiency as well as in patients with a diagnosis of Buerger's disease. 19 Theander demonstrated stationary arterial waves, "a string of pearls effect," in young patients with acute arterial embolism. 75 Wickbom noted "small circular constrictions" in vessels in which a catheter and metal guide were inserted and noted their disappearance after injection of Priscoline. B4 He found these constrictions in patients with Raynaud's phenomenon, tumor, and atherosclerosis, as well as in patients with Buerger's disease. Lindbom, after noting spasm in arteriograms and in some instances many short circular constrictions, concluded that "the arterial wall should be judged arteriographically with great caution in cases in which a catheter or another object is or has been present in the lumen and in which the vessel is suddenly dilated by forceful injection."42 More recently, Kohler has stated that it is difficult to find a physical explanation for the arteriographically demonstrated regular, alternating changes in arterial width. The most likely cause of the changes is spastic circular constrictions in the vessel. wall induced by irritation from the contrast medium in subjects with especially sensitive vessels. Although Kohler believes that very slight constrictions may be difficult to distinguish from diffuse intimal thickenings, the appearance causes no problems in differential diagnosis in typical cases. 39 Dr. Noah Susman of the Radiology Department of the Jewish Hospital of St. Louis has recently reviewed a small number of unselected
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arteriograms of the lower limbs and observed the "rippling" phenomena in roentgenograms of five patients. Two were young men with atherosclerosis of the aortoiliac area with rippling of the superficial femoral arteries. One was a young woman who had a femoral arteriogram to delineate the blood supply of a calf tumor; another was a young man in whom arteriography was performed to demonstrate a traumatic injury to the popliteal artery. Rippling of the femoral artery was observed in both patients. The fifth patient was a young man who presented with a chief complaint of leg cramps at rest and who exhibited good peripheral pulses: his arteriogram showed rippling but no obstruction of the femoral artery. It would appear therefore that the rippling effect described by McKusick is not unique to patients with Buerger's disease and that the uncertainty of Szilagyi in the diagnosis of thromboangiitis obliterans is not dispelled by its presence.
BUERGER'S SYNDROME It is now widely agreed that in the past the term Buerger's disease was loosely applied to young men with peripheral arterial insufficiency from diverse causes. The vast majority developed their symptoms and signs secondary to peripheral atherosclerosis. There were also a few young men mislabeled as having thromboangiitis obliterans who developed their ischemia secondary to endocardial mural thrombi and still another group in whom the ischemia resulted from an arteritis distinct from that described by Buerger. Evidence previously presented by us has clearly demonstrated that Buerger himself only rarely found proof that the patients he studied had thromboangiitis obliterans,82 an observation that should put to rest the claim that Buerger's disease was a more common entity before 1930 than it was after that date. The argument for the existence of Buerger's disease as an entity is, in fact, reduced to a constellation of clinical findings noted by many observers 27 • 33. 64 and effectively characterized as the Buerger syndrome by McKusick: "Regardless of whether one accepts Buerger's disease as an entity, one cannot question the existence of a clinical syndrome which can with historic justice be termed the Buerger syndrome: occlusive peripheral vascular disease, that occurs almost exclusively in men. It begins before 35 years in most, and before 20 years in some. In many, it affects the arms as well as the legs; it occurs almost solely in tobacco smokers; it demonstrates an intimate relationship of remission and relapse to cessation or resumption of smoking; and it manifests excruciating pain out of proportion to that found in other forms of peripheral vascular disease. In many, it is associated with migratory thrombophlebitis, but it is not associated with diabetes mellitus, hypercholesterolemia, or heart disease, which might be the source of emboli."51 There are few physicians who have not seen patients fitting this description. But how specific are these findings? Silbert, in spite of the fact that he reported on perhaps the largest clinical series of patients with Buerger's disease, denied the existence of any pathognomonic clinical finding and stated that the diagnosis could only be made after
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other causes of arterial insufficiency had been excluded. 67 Moreover, when causes of arterial obstruction other than thrombosis are excluded, in what way are those rare cases labeled Buerger's syndrome distinguished from other patients with thrombosis to whom the eponym has not been applied?
RECONCILIATION When the investigators at the Boston Beth Israel Hospital concluded the disease originally described by Buerger is indistinguishable from atherosclerosis, systemic emboli, or peripheral arterial or venous thrombosis, singly or in combination,82 McKusick took exception to this allinclusive phraseology. He observed that "since all occlusive vascular disease is, in the last analysis, thrombosis, the latter part of the statement is difficult to refute."51 So, indeed, it is. Therein lies a resolution to the recent controversy concerning the identity of thromboangiitis obliterans. These uncommon patients, who fit the Buerger syndrome, can be considered to have idiopathic peripheral arterial thrombosis, possibly on the basis of systemic hypercoagulability or secondary to some immunologic disorder, as suggested by others in the past. 29 • 40. 43.77. 81 Idiopathic arterial thrombosis differs from its counterpart in the veins largely by its relative rarity, a difference accounted for in part by the comparative ease with which venous flow may be retarded. My original demurrer was to accepting what Buerger described as a specific disease. My current reservation toward the term Buerger's syndrome is that it potentially subdivides an already idiopathic group and does not thereby clarify whether the terms Buerger's syndrome and idiopathic peripheral arterial thrombosis are synonyms or describe different entities. If they are the former, then the advantages of the term are not clear; if the latter is true, then one must ask what the syndromes that describe the remaining patients with arterial thrombotic disease are. My personal conjecture is that the term Buerger's syndrome is presently being used as an umbrella for the occasional patient with peripheral arterial thrombosis the cause of which is unknown. The semantics of this terminology will not, of course, be settled by debate. For after all the substantive issue concerns the factors initiating arterial thrombosis, not the label of the consequence of the obstructionso long as the label does not obscure the nature or the management of the underlying biologic problem. If this reasoning is valid, can there be any advantage in discarding the term Buerger syndrome, which memorializes an investigator whose stimulus to the study of the peripheral circulation was unique? One rather practical concern presents itself, namely, that we may protect patients from treatments still recommended for the therapy of Buerger's disease that are not suggested for patients with arterial insufficiency from other causes. Even though intravenous injections of saline and diets free of rye bread are no longer prescribed, the therapeutic armamentarium still includes malarial therapY,17 bilateral adrenalectomy,58. 80 hyperbaric oxygen,48 tolbutamide,68 phenylbutazone and prednisone. 54
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As for the claim that patients with Buerger's disease have a better prognosis than those with peripheral atherosclerosis,52 would not the patient with idiopathic peripheral arterial thrombosis also have a better outlook than the individual with ischemia secondary to atherosclerosis?
REFERENCES 1. Abramson, D. I.: Diagnosis and treatment of thromboangiitis obliterans. Geriatrics, 20:28, 1965. 2. Abramson, D. 1., Zayas, A. M., Canning, J. R, and Edinburg, J. J.: Thromboangiitis obliterans: A true clinical entity. Amer. J. Cardiol., 12:107, 1963. 3. Allen, E. V., and Brown, G. E.: Thromboangiitis obliterans: Clinical study of 200 cases: Etiology, pathology, symptoms, diagnosis. Ann. Int. Med., 1 :535, 1928. 4. Barker, N. W.: The case for retention of the diagnostic category "thromboangiitis obliterans." Circulation, 25: 1, 1962. 5. Bernheim, A. R, and London, 1. M.: Arteriosclerosis and thromboangiitis obliterans: Report of cases and treatment. J.A.M.A., 108:2102, 1937. 6. Boyd, A. M., Ratcliffe, A. H., Jepson, R P., and James, G. W. H.: Intermittent claudication: Clinical study. J. Bone Joint Surg., 31B:325, 1949. 7. Brown, G. E., and Allen, E. V.: Thromboangiitis obliterans: Clinical, physiologic and pathologic studies: Collaborating in pathology, with Howard R Mahomer. Philadelphia, W. B. Saunders Company, 1928. 8. Buerger, L.: Association of migrating thrombophlebitis with thromboangiitis obliterans. Internat. Clin., s. 193:84, 1909. 9. Buerger, L.: Concerning vasomotor and trophic disturbance of upper extremities, with particular reference to thromboangiitis obliterans. Amer. J. Med. Sc., 149:210, 1915. 10. Buerger, L.: Pathology of thromboangiitis obliterans. Med. Rec., 97:431, 1920. 11. Buerger, L.: Recent studies in pathology of thromboangiitis obliterans. J. Med. Res., 31 :181,1914-1915. 12. Buerger, L.: The circulatory disturbances of the extremities: Including gangrene, vasomotor and trophiC disorders. Philadelphia, W. B. Saunders Company, 1924. 13. Buerger, L.: Thromboangiitis obliterans: Concepts of pathogenesis and pathology. J. Internat. Chir., 4:399, 1939. 14. Buerger, L.: Veins in thromboangiitis obliterans, with particular reference to arteriovenous anastomosis as cure for condition. J.A.M.A., 52: 1319, 1909. 15. Buerger, L., and Kalinski, D. J.: Complement-fixation tests in thromboangiitis obliterans. Med. Rec., 78:665, 1910. 16. Buerger's disease. (Editorial.) Brit. Med. J., 2: 1214, 1960. 17. Corelli, F.: Buerger's disease. (Letter.) Brit. Med. J., 1 :209, 1961. 18. Craven, J. L., and Cotton, R C.: Haematological differences between thromboangiitis obliterans and atherosclerosis. Brit. J. Surg., 54:862, 1967. 19. DeBakey, M. E., Crawford, E. S., Garrett, H. E., Cooley, D. A., Morris, G. C., and Abbott, J. P.: Occlusive disease of the lower extremities in patients 16 to 37 years of age. Ann. Surg., 159:873, 1964. 20. DeTakats, G.: Classification of Buerger's disease. (Letter.) New Eng. J. Med., 263:412, 1960. 21. Dible, J. H.: Does Buerger's disease exist? (Letter.) Lancet, 2: 1138, 1960. 22. Does Buerger's disease exist? (Editorial.) Lancet, 2:969, 1960. 23. Diirch-Miinchen, H.: Die sogenannte "Thrombangiitis obliterans" im Rahmen der infektios-toxischen Gefassentzundungen. Verhandl. d. deutsch. path. Gesellsch., 25: 272, 1930. 24. Enos, W. F., Holmes, R H., and Beyer, J.: Coronary disease among United States soldiers killed in action in Korea: Preliminary report. J.A.M.A., 152:1090, 1953. 25. Fisher, C. M.: Cerebral thromboangiitis. Medicine, 36:169,1957. 26. Gery, L., Fontaine, R, and Branzeu, P.: Les lesions chroniques obliterantes des arteresdes membres: (estude anatomo-clinique). J. Internat. Chir., 4:427, 1939. 27. Goodman, R M., Elian, B., Mozes, M., and Deutsch, V.: Buerger's disease in Israel. Amer. J. Med., 39:601, 1965. 28. Gore, 1., and Burrows, S.: Reconsideration of pathogenesis of Buerger's disease. Amer. J. Clin. Path., 29:319, 1958. 29. Gruber, G. B.: Endarteritis obliterans und Kiiltebrand. Beitr. z. path. Anat. u. z. allg. Path., 84:155, 1930. 30. Hall, E. M.: Blood and lymphatic vessels. In Anderson, W. A. D. (ed.): Pathology. 3rd edition. St. Louis, C. V. Mosby Co., 1957, p. 521. 31. Harkavy, J.: Tobacco sensitiveness in thromboangiitis obliterans, migrating phlebitis and coronary artery disease. Bull. N.Y. Acad. Med., 9:318, 1933.
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