Br J Vener Dis: first published as 10.1136/sti.24.3.104 on 1 September 1948. Downloaded from

GANGRENE OF THE TOES IN . DESCRIPTION OF A CASE WITH A CRITICAL REVIEW OF THE LITERATURE BY E. J. MOYNAHAN Dermatological Registrar, Guy's Hospital; late Specialist in VenereolQgy, Royal Air Force Stokes and others (1944) state that syphilis of the between syphilis and arterial , but paid more arteries of the extremities is comparatively uncom- attention to its cutaneous, mucosal, and osseous mon, and that syphilitic thrombosis and endarteritic manifestations. There were two notable excep- changes in the arterioles are rarer still. In the tions. Lancisi (1654-1720) noted the frequent current standard work on peripheral vascular occurrence of aneurysms, -and in his work "De (Allen, Baker, and Hines, 1946) there is motu cordis et aneurysmatibus," published in Rome merely passing reference to syphilis of the peripheral in 1728, after his , he discussed " aneurysma vascular tree; the literature on peripheral vascular gallicum," thus clearly recognizing the role of syphilis reviewed in the present paper is scanty, and syphilis in the production of aneurysms. Morgagni the evidence presented does not always support the (1682-1771) gave a clear description, of the macro- authors' claims to have established a diagnosis of scopic changes produced by syphilis in the aorta syphilitic arterial disease. Further, there is a and the great vessels and had no doubts as to their conflict of opinion between some pathologists, origin. copyright. notably Warthin (1922) and Saphir (1929), and the Nevertheless, in spite of Morgagni's eminence as majority of clinicians as to the relative incidence of- a morbid anatomist, the relationship between syphilitic lesions in the peripheral vascular system; syphilis and cardiovascular disease continued to some deny that such lesions occur. In view of this be ignored until nearly a century after his death. it is considered that the occurrence ofgangrene ofthe John Hunter helped to perpetuate this ignorance toes in a syphilitic patient is worthy ofrecord. by stating in his book on aneurysms that he had never seen the brain, the heart, or the great vessels

Historical Survey involved in syphilis. Such was the weight of http://sti.bmj.com/ The history of arterial syphilis may be said to Hunter's authority that it was not until the middle begin with Vesalius (1514-64), who was the first to of the last century that his views were shown to be- recognize an aneurysm ofthe thoracic and abdominal erroneous. In 1849 Dittrich published his memoir aorta in a living patient. The diagnosis was con- in which he described the changes he found in the firmed two years later at but he failed to carotid and sylvian arteries in a syphilitic patient;. associate it with syphilis. Ambroise Pare was the he correctly attributed the changes to syphilis. first to suggest syphilis as a of aneurysm Soon afterwards, Sir Samuel Wilks (1863), the on September 26, 2021 by guest. Protected (Garrison, 1929), and Jean Fernel also suspected distinguished Guy's physician, showed that arteritis. th4e relationship between the two conditions. In played the major role in the cerebral accidents his classic Latin poem " Syphilis sive Morbus which may occur in syphilis. Gallicus," Fracastoro (1483-1553) does not mention Twelve years later, in 1875, F. H. Welch, in a the effects of syphilis on the peripheral vessels, paper entitIed "On aortic aneurysm in the Army unless one construes and the conditions associated with it," definitely established the relationship between aneurysmal " .. . membris exangibus, atque lacertus dilatation of the aorta and syphilis. Welch was. Inde graves dabat articulus extenta dolores." then assistant Professor of at the Army (lines 345-346 in Wynne-Finch's edition) as indica- Medical School, Netley, but his fundamental ting the clinical picture of of the limbs: contribution remained unrecognized. It was not but the context does not allow this. until the work of Doehle, twenty years later, that In general the physicians of the sixteenth and the profession as a whole accepted the wtiological seventeenth centuries did not suspect the connexion role of syphilis in the production of aortic aneurysm. 104 Br J Vener Dis: first published as 10.1136/sti.24.3.104 on 1 September 1948. Downloaded from

GANGRENE OF THE TOES IN SYPHILIS 105 That syphilis might produce peripheral vascular Letulle and others (1925) described a case of disease was not suspected until late in the nineteenth intermittent claudication in a syphilitic patient with century. The clinical and pathological knowledge lesions of the aorta, iliac arteries, and vessels of the existing then, however, was not complete enough legs. They considered that the lesions found in the to avoid confusion between syphilitic and non- tibial arteries were those of a syphilitic arteritis syphilitic affections of the limbs. As a result, similar to that found in lues of the cerebral arteries. syphilis was held responsible by some authors Saphir (1929), in a study of fifty cases of syphilitic (Darier, 1904), for conditions which would not aortitis, examined at autopsy the innominate, now be considered syphilitic. The discovery by common carotid, superior and inferior mesenteric, Schaudinn and Hoffmann in 1905 of the Spirochata and common iliac and femoral arteries for evidence pallida as the causal organism of syphilis paved the of syphilitic disease. He considered that an way for Warthin's work on syphilitic disease of the endarteritis obliterans of the vasa vasorum of the peripheral vessels. His work did not appear until adventitia of the aorta, accompanied by perivascular after the world war 1914-18, and, although it is not infiltration with lymphocytes, is the earliest mani- fully accepted by many clinicians, it may be regarded festation of syphilis in the aorta. He adopted these as the first scientific contribution to our knowledge criteria for evidence of early syphilis in the vessels. of the pathology of syphilis as it affects the arteries, He interpreted interruption of the elastic lamellk other than the aorta, its main branches, and the of the media by round-cell infiltration or connective cerebral arteries. The present century has seen a as a later manifestation of the syphilitic great increase in our clinical understanding of process. Changes which he considered to be peripheral vascular disease, and also the develop- characteristic of syphilis were found more fre- ment of accurate methods for their investigation. quently in the vasa vasorum of the larger vessels Consequently, precise diagnosis has become possible with a relatively rich tunica elastica than in the in the majority of cases showing symptoms of smaller vessels with their relatively rich musculature. peripheral vascular disorder. Nevertheless, syphilis By these standards he found evidence of syphilis: is an exception, and the clinical diagnosis of peri- in 33 out of50 innominate arteries examined copyright. pheral vascular syphilis can usually be arrived at in 29 out of50 carotid arteries examined only by exclusion. in 15 out of29 subclavian arteries examined Review of the Modern Literature in 10 out of 50 common iliac arteries examined in 10 out of50 superior mesenteric arteries Doehle (1895) was the first to recognize and examined describe the of syphilitic aortitis. in 3 out of50 inferior mesenteric arteries He stated that the condition began with a examined round-cell proliferation in and around the vasa

in 7 out of50 femoral arteries examined. http://sti.bmj.com/ vasorum of the adventitia of the aorta, extending later to the media with consequent damage to the Lian and others (1931) considered the role of elastic tissue of the wall and eventual aneurysm syphilis to be under-estimated in arterial disease. formation. In a discussion of arteritis obliterans of the lower Warthin (1922) held that syphilis affected the limbs, they state that most cases of gangrene in the peripheral arteries in a similar way. He claimed aged are due to a simple atheromatous change in to have demonstrated the presence of S. pallida in the vessels, but that stenosing changes at a younger the iliac, femoral, popliteal, and tibial arteries in age should make the clinician think of syphilis. on September 26, 2021 by guest. Protected cases of perforating , gangrene, symmetrical Herrmann (1933) states that we are unable to say gangrene simulating Raynaud's disease, and scler-- how often syphilis affects the peripheral arteries or osing . Warthin considered that the lesions to say with certainty if it does so at all. He recog- which he found in those medium-sized vessels were nized three clinical types which he called respectively essentially those of a mesarteritis. He thought the angiospastic, the endarteritic, and the thrombo- that the changes in the smaller arteries presented phlebitic. The angiospastic type affects the upper the appearances of a panarteritis, periarteritis, or limb, and manifests itself as a chronic arteriospasm proliferating arteritis. The lesions were seldom of with constant pain in the distal part of the affected any size and could be detected only by microscopic arm. Hermann thought that the vasospasm arose examination. It is not surprising that the existence reflexly from chronic irritation of the perivascular of these lesions, if in fact they do occur, had escaped nerve plexuses involved in the syphilitic process. notice, since the smaller vessels are rarely looked at, The endarteritic type presents clinically as inter- and still less frequently subjected to histological mittent claudication, and this he attributed to an examination at autopsy. obliterative endarteritis of the terminal and smaller Br J Vener Dis: first published as 10.1136/sti.24.3.104 on 1 September 1948. Downloaded from

106 BRITISH JOURNAL OF VENEREAL DISEASES arterioles. The thromboarteritic type exhibits itself (1946) state that in an experience extending over by extensive occlusion of all the major arterial many years they never saw peripheral vascular pathways without gross gangrene. disease due to syphilis. Derrick and Hass (1935) described a case of diffuse arteritis which they considered to be of Case Report syphilitic origin. The patient was a young man in An aircraft hand, aged 31 years, was transferred to a arteritic changes were found in the small Royal Air Force Special Treatment Centre on Aug. 15, whom 1943, with the following history. Whilst he was under- vessels of the gut, liver, pancreas, kidneys; and going his recruit's training course he complained of a adrenals, with occlusion of the vessels either by painful ingrowing toe-nail on his right great toe. He marked thickening of their walls, formation of was seen by a surgeon and was shortly afterwards thrombi, or a 'combination of both processes. admitted to an E.M.S. Hospital, where the toe-nail was There were numerous infarcts in the affected organs. removed. A few'days after the operation he complained No lesions were found in the voluntary muscles or of pain in the toe, which was found to be gangrenous and in the skin. Spirochletes were found only in some the terminal phalynx was removed. Within forty-eight areas of and in the duodenal hours of this, the fifth toe of the same foot became he died the patient had received gangrenous and had to be removed. Serological tests mucosa. Before were then done, and both the Wassermann and Kahn arsenotherapy and serological tests had become tests were positive. Before his transfer to the Special negative. The clinical picture they describe resem- Treatment Centre anti-syphilitic treatment with neo- bles that of polyarteritis nodosa, and apart from the arsphenamine and bismuth was begun. isolated finding of spirochites in the duodenal that syphilis was the On Admission.-Physical examination revealed a mucosa there is little to suggest moderately well-nourished man, who looked pale, ill, cause of the extensive arterial disease found in this and older than his years. Intelligence was below patient. They were emphatic that the spirochetes average; he was unco-operative, of a surly disposition, which they found were morphologically indistin- and answered questions reluctantly, but he was- well guishable from those of syphilis, but the serological orientated. He proved to be a difficult disciplinary tests were negative. Ifsyphilis had been responsible problem, and he absented himself without leave- and for the arterial changes one would have expected refused to submit to most of the investigations which copyright. to find the spirochete in many of the vessels and the would have amplified this case report. serological tests should have remained positive. It Mouth.-Hygiene was poor, the teeth deficient and must be concluded, therefore, that the authors are neglected, the mucoswe pale, the fauces clear. There was in error and that the probable diagnosis in this case no glandular enlargement and no evidence of congenital was polyarteritis nodosa. lues. Grauer and Myers (1944) described a case of Cardiovascular System.-The heart was normal in peripheral vascular syphilis involving the vessels of size, shape, and position, with no bruits. Blood pressure the legs in a white soldier of the U.S. Army. This was 120/60 mm. Hg. The pulse was regular. Brachial, http://sti.bmj.com/ "Ulcer on the plantar radial, and ulnar arteries were normal, and the pulses man developed a small painful equal on both sides. There were no trophic changes in surface of his fourth right toe, which was eventually the hands. The femoral arteries of the legs and the amputated. Further lesions developed on his right popliteal arteries appeared normal, with pulses equal. foot after the toe had been amputated, and it was the volume of the popliteal arteries was good. Neither only then that a serological test (Wassermann) was dorsalis pedis artery could be felt and there was only done. This was found to be positive. The pulse faint pulsation in the posterior tibials. ofthe dorsalis pedis artery could not be felt on either Central Nervous System.-The pupils were equal and on September 26, 2021 by guest. Protected side. The anterior tibial pulses on both sides were concentric. They were small, but reacted to light and also absent. A course of mapharsen and bismuth on convergence. The fundi appeared normal but was given, with an excellent therapeutic response. arteries looked rather narrow. There was left facial The authors conclude that syphilitic peripheral weakness and weakness of the right twelfth nerve. The superficial and deep reflexes were present and equal on vascular disease presents little that is distinctive on both at both sides. The plantar response was flexor clinically, and that the diagnosis can be arrived sides; there was no sensory loss or disturbance. only by a process of exclusion. A study of the Other f+stems appeared normal. The urine contained literature as well as personal experience makes one no sugar or albumin. The blood Wassermann and endorse this view, which sums up the present status Kahn reactions were strongly positive. The cerebro- very well. spinal fluid was not examined as the patient refused Learmonth (1944), in a review of peripheral lumbar puncture. vascular disorders, mentions syphilitic arteritis as Feet.-The right fifth toe, and the terminal phalanx of one of the conditions which may produce the right great toe were missing, and the scar and wound of a limb or part of a limb. Leriche and Bertrand were healing slowly. The foot was pale but there was Br J Vener Dis: first published as 10.1136/sti.24.3.104 on 1 September 1948. Downloaded from

GANGRENE OF THE TOES IN SYPHILIS-107107 no cyanosis and it was not cold. The left foot appeared the case inder consideration, both. the neurological normal. signs and the gangrene could have been attributed Discussion and Differential Diagnois to periarteritis nodosa. This diagnosis was thought to be unlikely in view of the otherwise negative In the case described above there can be little fndings and the fact that a diagnosis of syphilis doubt concerning the cause of the neurological accounted more satisfactorily for the neurological findings. They are not uncommon -in cerebro- signs. The good response to anti-syphilitc treatment vascular syphilis. It is more difficult to establish -was 4lso considered to weigh against this diagnosis, that the gangrene ofthe toes was due to syphilis, but it should be borne in mind that long remissions and in order to do so it is necessary to consider the have- been reported in some undoubted cases of other causes of gangrene. The following conditions periarteritis nodosa. were considered, as- they must be in every case of gangrene arising in a syphilitic patient, before the Acute Arterial Embolism.-By -failure to find any ,conclusion was reached that syphilis was responsible of the common conditions in which this might arise, for the loss of this patient's toes. acute arterial embolism was dismissed as a cause of Diabetic Gangrene.-This could be excluded by gangrene in this patient. In particular,- there was the normal urinary findings. In doubtful cases a no evidence of auticular fibrillation, myocardial sugar tolerance curve may be required, but it was not -infarct, or bacterial endocarditis ;- -neither was necessary here. there any sign of aneurysm affecting the wall of any vessel in the limb showing gangrene. Raynaud's Disease.-This was ruled out by the history. Furthermore, this malady is much com- Arterial Thrombosis.-Arterial thrombosis was moner in women, and in practically every case the considered but rejected as the cause of the peripheral upper limbs are involved. The peripheral arterial vascular changes. None of the predisposing causes pulses are always present in Raynaud's disease, but was present. These include acute , blood were not felt in this patient. There is usually diseases-particularly leukemia and polycythrmia- bilateral and symmetrical involvement of the limbs, thrombo-angiitis obliterans, periarteritis nodosa, copyright. ;and gangrene, if present, is nearly always slight. disseminated lupus erythematosus, and sclerodermia. Raynaud's disease never presents with gangrene of Traumatic Gangrene. -Traumatic- gangrene such the toes as a first symptom. as follows injury to the main vessel of a limb could Arteriosclerotic Gangrene.-This usually occurs in obviously be excluded in the absence of any such males over 50. Calcified arteries are frequently -injury. The trauma of the operation, however, present, and can be felt or demonstrated by radio- may well have determined the onset of gangrene in graphy. There was no clinical evidence of arterio- this patient; and it is probable that without this http://sti.bmj.com/ sclerosis in this case. added burden to the- impaired circulation in his toes, necrosis would not have occurred. The post- Thromnbo-angiitis Obliterans (Buerger's Disease).- operative inflammatory response proved too much This is not uncommonly the cause of gangrene of for the diseased vessels and led-to thrombosis, -with the toes in patients ofhis age and sex. Further, our consequent ischiemia, of the terminal digital arteries. patient had asymmetrical -gangrene involving the lower limb with absent peripheral pulses, a picture Toxic Gangrene.-Gangrene resulting from ergo- tism or arsenical poisoning could obviously be which would fit in well with a diagnosis- of Buerger's on September 26, 2021 by guest. Protected disease. However, there was no history of inter- excluded in the absence of any history of his taking mittent claudication or other symptoms ofperipheral these substances. Chemical gangrene, such as impairment. The patient was an Irishman, a race might follow the application ofa dressing containing in which few cases of the malady have been reported. phenol, could also be excluded. Periarteritis Nodosa.-This may cause gangrene Cryopathic Gangrene.-Gangrene due to of the toes or part of a limb. It may also give rise or other effects of cold obviously did not need to be to neurological signs. Usually the whole clinical considered. picture is bizarre, with , weakness, loss of Syphilis is the only cause left, after excluding the weight, alburninuria, hypertension, and eosinophilia foregoing, to account for the occurrence of gangrene as the commonest findings. There is no constant in this patient. This is the only conclusion that can clinical picture,-and the diagnosis is often made only be drawn from the history, clinical signs, and sero- at autopsy. The disease usually affects many logical findings.. It may be assumed that the arteries, so that it can mimic a large number of removal of his ingrowing toe-nail merely coincided maladies. It is becoming evident, too, that the with a phase in his syphilitic when there disease may be confined to a few vessels, so that, in was a widespread involvement of his arteries. The D Br J Vener Dis: first published as 10.1136/sti.24.3.104 on 1 September 1948. Downloaded from

108 BRITISH JOURNAL -OF VENEREAL DISEASES trauma of the operation, occurring at this phase of heavy metal, arsenic, or sulphonamide therapy his disease, may therefore be regarded as the prior to the onset of symptoms, since some cases of precipitating factor. It is reasonable to presume polyarteritis have been attributed to drug allergy; that, had he not been operated on at that particular (7) the urine should not contain sugar; (8) there time, gangrene would not have ensued although he should be a satisfactory response to appropriate would have developed the neurological manifesta- anti-syphilitic therapy. tions of syphilis which did in fact show. The diagnosis can be confirmed in one way only,' It is unfortunate that, owing to his refusal to that is, the demonstration of spirochztes in the submit to further investigation and also to lack of affected vessels. This has rarely been accomplished, facilities for a more thorough study of his peripheral so that in most cases the diagnosis of peripheral vessels, unequivocal proof of the syphilitic origin of vascular syphilis is one that can be arrived at only his gangrene could not be obtained. In particular, by excluding the other causes of arterial disease. the following investigations omitted in the study of this case might have produced conclusive proof REFERENCES of the syphilitic nature of the changes in the arteries Allen, E. V., Barker, N. W., and Hines, E. A. (1946). of his foot: (a) histological examination of the " Peripheral Vascular Disease." W. B. Saunders. tissues removed at , and (b) biopsy of Philadelphia and London. Darier, J. (1904). " De l'Art6rite Syphilitique." Ruliff. the tissues ofthe foot. The sections obtained should Paris. be stained'for spirochaetes, because it is necessary Derick, C. L., and Hass, G. M. (1935). Amer. J. Path., to demonstrate their presence before one can be 11, 291. certain that the changes seen are in fact due to Doehle, K. G. (1895). Dtsch. Arch. klin. Med., 55, 190. Erichsen, J. E. (1844). " Observations on Aneurysm." syphilis. This must be regarded as of crucial Sydenham Society. London. importance in any study of syphilitic disease of the Fracastoro, G. " Syphilis, or the French Disease." peripheral vessels, because the histological changes Trans. by Wynne-Finch, H. (1935). Heineman. in themselves are not specific. London. Garrison, F. H. (1929). " Introduction to the History copyright. Conclusion of Medicine." Fourth Edition. W. B. Saunders. Philadelphia and London. The study of the literature and experience in the Grauer, F. H., and Myers, H. L. (1944). Amer. J. Syph., clinic show that gangrene of a digit due to syphilis 28, 458. is an extremely rare event. There are no patho- Herrmann, L. G. (1933). Ibid., 17, 305. in peripheral vascular syphilis, but Learmonth, J. R. (1944). Brit. med. Bull., 2, 136. gnomic signs Leriche, R., and Bertrand, I. (1946). " Thromboses certain criteria should be fulfilled before a diagnosis Art6rielles." Masson et Cie. Paris. of peripheral vascular syphilis is 'made. These are: Letulle, M., Heitz, J., and Magniel, M. (1925). Arch. (1) positive serological tests," repeated more than Mal. Caeur, 18, 497. http://sti.bmj.com/ Lian, C., Blondel, A., Barrieu, R., and Ribas Soberano, once; (2) signs of clinical activity elsewhere; F. (1931). Paris mid., 2, 21. (3) the patient should be under 50 and should show Saphir, 0. (1929). Amer. J. Path., 5, 397. no signs ofarteriosclerosis; (4) the diastolic pressure Stokes, J. H., Beerman, H., and Ingraham, N. R. (1944). should not exceed 90 mm. Hg., thus excluding all " Modern Clinical Syphilology." W. B. Saunders, Philadelphia and London. hypertensive cases and many of polyarteritis Warthin, A. S. (1922). N. Y. med. J., 115, 69. nodosa; (5) the blood picture should be within the Welch, F. H. (1875). Med. Chir. Trans., Lond., 41, 59. normal range; (6) the patient should have had no Wilks, S. (1863). Guy's Hosp. Rep., 9, (ser. 3), 1. on September 26, 2021 by guest. Protected