cardiovascular syphilis. - a global journal from bmj · cardiovascular syphilis, especially in the...

VII

CARDIOVASCULAR SYPHILIS. I.

A RESUM1: AND COMMENTARY

By E. TYTLER BURKE, D.S.O., M.B., Ch.B.

THE subject of syphilis as it affects the heart andvessels is one which has of recent years been graduallyattracting an increasing meed of attention from clinicianand pathologist alike. Indeed, it bids fair to oust neuro-syphilis from the prominent position occupied for so longby that condition. The present appears to be an oppor-tune time to attempt a brief review of cardiovascularsyphilis if for no other reason than the fact that at theforthcoming Annual Meeting of the British MedicalAssociation at Manchester in July the subject has beensingled out for special attention. It is to be discussed bythe Section of Medicine; and in the Section of VenerealDiseases, Professor Warthin, of the University ofMichigan, is to be the reader of a paper on " TheLesions of Late Syphilis," and it is inevitable that thecirculatory system will come in for a great deal of con-sideration.Of all the regions of the human body there is none

wherein there lurks more unsuspected syphilis than thecardiovascular system. That the vessels certainly, andthe heart probably, are involved in every case of syphilisis clear when once the essential pathology of the diseaseis appreciated. Unfortunately, however, this apprecia-tion is by no means general; and it follows therefromthat much of the treatment administered is inadequate inquantity, in quality, or in both. The results of formertreatment which are seen, for example in the practice ofa large venereal diseases clinic, illustrate this only toowell. Such a state of affairs invariably follows whentherapy is based upon unsound pathology.That syphilis is so common a cause of cardiac derange-

ment and vascular damage is insufficiently recognised inI38

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CARDIOVASCULAR SYPHILIS

general practice. Indeed, to a certain degree this alsoapplies to hospital out-patient work, except, of course,in the special cardiological departments. Examinationparticularly directed to the circulatory system of syphiliticpatients attending a treatment centre will show a sur-prising amount of cardiovascular involvement in thoseunder treatment, and of permanent damage in those whoare clinically and serologically cured. It would appear tobe necessary to lay strong emphasis upon the facts thatn every case of syphilis the vessels are affected from thevery beginning, that the heart becomes involved at amuch earlier stage than is generally realised, and thatunless treatment is dictated by modern pathologicalknowledge, permanent damage is likely to be inflictedupon the circulatory system and a condition of endo-syphilis be set up.The modem pathological view is that syphilis is essen-

tially a disease of the blood vessels. The circulatorysystem is the chosen canvas upon which the Treponemapallidum spreads its multifarious pigments. The basicand distinctive tissue lesion of syphilis is a microscopicone. In all stages and in all organs it is in its essenceidentical. It begins in the perivascular lymph spaces asan infiltration of lymphocytes and plasma cells. Allluetic manifestations are but varying degrees of this tissuereaction evoked by the Treponema pallidum, and modifiedaccording to the tissue or organ affected. All syphilis,from the alpha of the initial sclerosis to the omega ofthe final necrosis, has an underlying basic vascularelement.The plasma cell would appear to be the descendant of

the lymphocyte and the ancestor of the fibroblast. Twotypes of involvement are to be distinguished in the latelesions of syphilis. Both commence in the same fashion-an early endarteritis succeeded by a periarteritis-butthey differ in their end-results. In the one, the conditionis an interstitial fibrosis proceeding sometimes to theformation of numerous miliary gummata. The fibrosisis replaced by scar tissue, which may eventually becomecalcareous. This is the type which gives rise to cirrhosis.The second type differs mainly in degree from that justdescribed. The essential process remains the same. Thefinal stage in this latter condition is the formation of grossnaked-eye gummata with ulceration. It is important to

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BRITISH JOURNAL OF VENEREAL DISEASES

note that in the case of the heart muscle the inflammationis not invariably interstitial. It may primarily involvethe actual muscle fibres.The new pathology of syphilis dates from the dis-

covery of the Trcponema pallidum; but it was not untilthe publication of Warthin's work that it was clearly setforth. To his genius, his accurate observation, and hispainstaking care, medical science, and especially syphilo-logy, owes a tremendous debt. It is greatly to be re-gretted that the histopathology of syphilis, with itsclinical and therapeutic implications, has not yet pene-trated into all the teaching schools. Much of the contem-porary work published upon syphilis betrays a lack offamiliarity with the modern pathology of the disease.The morbid anatomy of syphilis-and particularly of lateand of endosyphilis-is still in many quarters inseparablyunited to the gumma. "No gummata, no syphilis "appears to be the slogan. It is essential in these days,when assessing the value of any work relative to syphilis,that the first consideration to be taken into account isthe pathological criteria upon which the investigation isbased. Unless this is modern in character and built uponthe foundations laid down by Warthin, anything erectedthereon is practically valueless. While giving full honourto the Old Masters of Pathology, it is idle to deny that theconception of syphilis as envisaged by Morgagni, Virchow,Rokitanski, Wagner, and Bauimler is obsolete and mis-leading. Unfortunately, it has not yet been erased fromall the text-books, and, in consequence, much clinical andtherapeutic work continues upon wrong lines. There arestill clinicians-and perhaps pathologists too-whosecamp is still pitched under the shadow of the gumma.The fact is that the overwhelming proportion of lueticinfections run their course without. gummatous forma-tion. The type-lesion of the diseasc-first, last, and allthe time-is that of a mild inflammatory process cha-racterised by an infiltration of lymphocytes and plasmacells, particularly in the stroma around the blood vesselsand lymphatics. Slight tissue proliferations subse-quently occur, and these proceed eventually to fibrosis,with atrophy and degeneration of the parenchyma.

Contrary to what appears to be the general conception,the majority of syphilitics who die from their diseasesuccumb not to locomotor ataxia or paresis, but to

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cardiovascular syphilis, especially in the form of chronicmyocarditis. The best index of the progress or regress ofsyphilis in the country is afforded not by the mortalityfigures for tabes and general paralysis, but by those fromcardiovascular disease as worked out by Osler. Onlyrarely do sufferers from syphilis die from central nervoussystem involvement.

Probably from the very earliest clinical evidences ofsyphilis-certainly from the commencement of the so-called " secondary" period-onwards, microscopic lesionsare found in the heart and great vessels characteristic oftreponemal localisation and activity. These vary greatlyin degree of severity. In most cases, cardiac and vesselfibrosis can only be demonstrated by the microscope. Itis most likely to be found in the anterior wall of the leftventricle near the apex, the adjacent portion of theseptum, and the posterior wall of the left ventricle nearthe attachment of the mitral valve. Naked-eye evidenceof fibrosis may be present; but its absence is no criterionof the non-existence of syphilis. In most of the post-mortem studies done in this country, the presence orabsence of the disease is decided by gross rather than bymicroscopic evidence. Such antiquarianism means thatonly an infinitesimal amount of post-mortem syphilis isuncovered, and this must react profoundly upon clinicalwork. The ubiquity of the disease is not appreciated;its clinical recognition is obscured; unduly optimisticprognoses are made; therapy lacks thoroughness; andit is not realised that even after the most prolonged treat-ment, the cardiovascular system of the average syphiliticwho is clinically and serologically cured is permanently" damaged goods." His grip upon life is appreciablyweakened.

In the early stage of generalised syphilis very evidentdisturbances of the cardiac rate and rhythm are common.In something like 50 per cent. of cases a definite bruit isto be made out. Brooks performed 50 consecutive post-mortems upon persons with cardiovascular syphilis andfound that in 28 cases the pericardium was involved, in44 the myocardium, gummata of the heart were found on5 occasions, while the coronary arteries were affected in35 instances. Warthin's experience is that in 85 per cent.of syphilitics who arrive at the post-mortem rcom, theheart is diseased.

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Cardiovascular syphilis may conveniently be classifiedin the following manner:

I. Pericarditis and epi- (I) Diffuse.carditis. (2) Localised (gumma).

(I) Parenchymatous.(2) Interstitial.

II. Myocarditis . . (3) Diffuse.(4) Involving bundle of

His.III. Endocarditis . . Aortic insufficiency.IV. Coronary arteritis.

(i) Without dilatation.V. Aortitis . . . a (2) Fusiform dilatation.

1 (3) Aneurism.(I) General arterioscle-

rosis (with or with-VI. Peripheral arteritis . out hypertension).

(2) Local arteriosclerosis.I(3) Aneurisms.(i) General.

VII. Peripheral phlebitis (2) Local with throm-bosis.

VIII. Vasomotor disturbance Raynaud's disease (?).

Pericarditis and Epicarditis.-Syphilitic pericarditis isapparently a much more common condition than clinicalexperience would suggest. Brooks found it in 50 percent. of luetic hearts. He described pericardial patcheswhich he likened to leucoplakia. An inflammation of thepericardium, usually too slight to secure clinical recogni-tion, is not infrequently found in association with aortitisand aortic aneurism. The occurrence of adhesions ordefinite pericardial thickening on the anterior aspect ofthe heart just above the apex is strongly suggestive ofsyphilis. Histological examination of the patch and ofthe subjacent myocardium will either confirm or deny thesuspicion.When so severe as to give rise to clinical signs, syphilitic

pericarditis presents of itself no specific diagnostic picture.The manifestations are those of an ordinary pericarditis;and it is only by a careful examination of the case fromevery angle that the syphilitic aetiology may be laid bare.Heirnann, Strachan, and Hayman in a preliminary note

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on cardiac disease among South African non-Europeansmention that syphilitic pericarditis, while sometimes seen,is rare. It appears as an effusion accompanied by failureof compensation, the clinical signs being those of peri-cardial effusion. Vigorous antisyphilitic therapy isstated to be sometimes successful. Donnison, in areference to Heimann's paper, mentions that he hasreported a case of syphilitic pericarditis which appearedto be a "gummatous pericarditis and myocarditis." Inexamining syphilitic patients I have occasionally heardat the apex fine crepitations systolic in time. These areoften intensified by pressure, and I am inclined to con-sider them at least suggestive of syphilitic pericarditis.As is mentioned by Osler and Gibson, an unusual form ofpericardial involvement is that in which the smallerpericardial arterioles are dotted with numerous smallaneurisms accompanied by much thickening of, andadherence between, the pericardium and epicardium.Syphilis of the mediastinum and pulmonary syphilis,especially at the root of the lung, may induce a peri-carditis.

Myocarditis.-In the parenchymatous variety, largecolonies of treponemata may be found when the tissue isstained by the Levaditi method. These colonies arechiefly seen in the tissue spaces and around the bloodvessels. They may give rise to no tissue reaction. Paledegeneration of the heart muscle may be seen which isof the nature of a liquefaction necrosis. Fatty degenera-tion may be the predominating or the sole conditionassociated with colonies of Treponema pallidum. Suchareas are focal and may be seen with the naked eye assmall yellowish spots. At times these are found to havebecome calcified. The specific change in the heart musclemay simply consist of atrophy of the muscle fibres. Inall these conditions Warthin was able to demonstrate thepresence of treponemata. The pale degeneration of themuscle substance is to be identified by the fact that thetissue fails to stain with eosin, and that the muscularstriations tend to disappear. Where the process isadvanced, it may be impossible to tell where muscle endsand connective tissue begins. In virulent congenitalcases, necrosis is present. The condition is quite inde-pendent from, or secondary to, any vascular condition.It is primary in character and is due entirely to the local

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reaction set up by the presence of large numbers oftreponemata.The interstitial type of proliferation is always peri-

vascular in origin, and it presents the characteristic histo-logical picture. CEdematous areas are present, especiallyin congenital cases, and so likewise are patches of myxo-matous degeneration. Both these are found to bethronged with treponemata. The interstitial infiltratedareas are but rarely focal or circumscribed. This servesin some measure to distinguish a treponemal from astreptococcal myocarditis.The whole thickness of the myocardium, not excluding

the papillary muscles, may be affected. As a rule, how-ever, the inflammatory area lies nearer to the endo-cardium, and it tends to spread more readily in thatdirection than deeper into the muscle. In congenitalcases, on the other hand, it is more common for the myo-carditis to begin nearer the epicardium and to progressstill further in that direction. In acquired syphilis, then,the usual course is for a myocarditis to progress towardsan endocarditis, while in congenital syphilis the conse-quence of myocarditis is more commonly a pericarditis.Some of the primary or so-called " idiopathic " cases ofpericarditis seen in children are manifestations of con-genital syphilis. It is important to keep congenitalsyphilis in mind as an aetiological factor in Pick's disease-pericardial pseudocirrhosis. In this condition, in additionto peritonitis, ascites, perihepatitis, and cirrhosis, there isoften in early life an adherent pericardium associatedwith chronic mediastinitis with adhesion between theepicardium and the pleura and chest wall. The result isgreat cardiac hypertrophy and dilatation.

Luetic myocarditis has been known to occur imme-diately after the appearance of the chancre and beforeany general cutaneous eruption. Recent observation andexperience seems to indicate that except in the very earlyprimary cases, myocarditis always occurs in some degree.It is the forerunner of pericarditis, endocarditis, valvulardamage, coronary arteritis, and aortitis in most, if not inall instances. To exaggerate its importance is almostimpossible; and the prudent attitude for the clinician toadopt is to regard every syphilitic with whom he iscalled upon to deal as suffering from syphilis of themyocardium. Treatment must be of such a character, be

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instituted at so early a date, and be pursued for so longa period that permanent damage to the heart muscle maybe avoided or minimised. Absolute certainty of fore-stalling myocardial fibrosis can only be assured by theprompt, vigorous, and prolonged treatment of syphilisimmediately upon the appearance of the initial. sore andbefore the serological test gives a positive result,When a patch of fibrosis reaches the surface of the

myocardium, the overlying epicardium or endocardiumbecomes thickened and roughened. Adhesions form, andtheir common site is just above the apex on the anteriorwall of the left ventricle. It is in this region that aneurismand rupture of the heart may occur.

In advanced cases of syphilitic myocarditis, the condi-tion is most marked around the smaller coronary arte-rioles. Syphilis appears to have a special' affinity forthese vessels, and they may show involvement evenbefore the appearance of the cutaneous eruption.Although it is probably true that in the majority ofcases the myocarditis, fibrosis, and necrosis is secondaryto coronary endarteritis, yet it has been conclusivelyshown that syphilitic myocarditis may be a primarycondition.

In its earliest stages syphilitic myocarditis is asympto-matic, but it is important that the thought of such anentity should enter the clinician's mind at the earliestpossible moment. Syphilis is a terribly un-originaldisease. It is, as Hutchinson said, " The Great Imitator."Its main characteristic is that it can produce in anyhuman tissue or organ, lesions which are more frequentlythe products of other diseases. Syphilis should alwaysbe eliminated before a diagnosis is made and therapycommenced. The routine serological test is long overdue.The certain signs of syphilitic myocarditis have yet to

be discovered, and at the present moment the clinicianmust grope his way through a jungle of indefinite twilight.In the past, perhaps, a little too much attention wasconcentrated upon the valves of the heart, and diagnosiswas chiefly taught by the differentiation of murmurs.Although it was emphasised by the earlier cardiologiststhat the heart muscle was all-important and that theprognosis of any cardiac affection depended upon thestate of the myocardium, yet that fact receded into theclinical background. It is only within comparatively

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recent years that the myocardium has received the atten-tion it deserves. Death is held off by the valour of themyocardium. Myocarditis is a cur that bites withoutpreliminary growling, whereas the loud bark of thevalvular bruit is very often edentulous.A certain degree of myocarditis is present in all patients

who progress beyond the early initial stages of syphilis.It may actually manifest itself contemporaneously withthe initial sclerosis. Hazen records a case occurring in aphysician where a serious myocarditis developed beforethe appearance of the rash. Tachycardia, arrhythmia,and intermittence are pointers for which to watch in theearly syphilitic. These by themselves are, of course, of noreal diagnostic value so far as syphilis is concerned, withrespect to persons presenting no other signs of thatdisease. Nevertheless, experience in their observationand in their disappearance under treatment has broughtconviction that they are of importance in the early stagesof the disease as indicating that the attack upon the hearthas commenced.

During the post-primary period of the disease, extra-systoles may be present. In early cases, these are some-times found to occur during the first week or two of treat-ment, which is somewhat suggestive that they may be ofthe nature of a Herxheimer reaction. Hypertension isalso sometimes developed under treatment in young sub-jects. Cardiac pain-or it may be merely a " heartsense "-is common. Harris found that pain was thepresenting symptom in 70 per cent. of his luetic heartcases.The electrocardiograph must surely prove of great

value; and it is probable that those who have the oppor-tunity for making extensive use of it may discover somepointers suggestive of, or perhaps even diagnostic of,syphilitic myocarditis. My personal experience of suchwork is so slight as to prevent me from speaking, butHarris gives it as his opinion that there is a type of elec-trocardiogram which is characteristic. He omits to givean illustration, but states that it consists of certainwavelets all over the electric line. There is some valuablework waiting to be done by collaboration between thevenereal diseases treatment centre and the cardio-logical department of a hospital. At the present time,how-ever, all that the electrocardiogram yields is a

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general statement as to the condition of the heart musclewithout any indication as to cause.

In auscultating the hearts of syphilitic patients there issometimes heard, especially in cases of several years'standing, a somewhat musical apical systolic bruit indi-cating mitral incompetence. This I believe to be due,no-t to any damage to the valve segments, but to afibrosis of the myocardium at the valve attachmentcausing a lack of coaptation of the segments with incom-plete closure.

Saggioro investigated the cardiac condition of twentypatients suffering from secondary syphilis. These wereall young men in whom circulatory disturbance due toage or alcohol could be ruled out. The conclusionsarrived at were: (I) that patches of myocarditis are therule in secondary syphilis; (2) that the usual symptomsare tachycardia and dyspncea; (3) that clinical examina-tion shows an enfeebled myocardium with frequently anincrease in the transverse diameter of the heart, irregularand small pulse, and blurred heart sounds; (4) thatmyocardial fibrosis may involve the terminal branches ofthe vagus nerve leading to disturbances of innervationwhich manifest themselves as extra-systoles, tachycardia,palpitation and an exaggeration of the oculo-cardiacreflex. The cardiac function should always be investi-gated bv the application of Katzenstein's test and theoculo-cardiac reflex. In the former, myocardial efficiencyis indicated by an increase of blood pressure during con-striction of the femoral artery. The latter reflex iselicited by firm compression of both eyeballs backwardsinto the orbits. Normally, this causes an immediateslowing of the heart rate by six to eight beats per minute,accompanied, it may be, by extra-systoles. The slowingceases immediately the pressure is removed.

Heart-block.-In dealing with this matter it is im-portant to keep in mind that heart-block and the Stokes-Adams syndrome are not different names for the samething. The former may occur without the syndrome,and it in turn may be due to causes other than disease ofthe auriculo-ventricular bundle. Heart-block is com-monly, but the Stokes-Adams syndrome only occasion-ally, due to syphilis. Heart-block is brought about byarteriosclerosis of the vessels supplying the bundle, byfibrosis or gumma of the bundle itself, or by pressure from

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adjacent fibrosis orgumma external to the bundle. Where,the condition is due to arteriosclerosis, little or nothing isto be hoped for from treatment. When the other condi-tions are operative, however, treatment is most effective.

In mapping out treatment it is essential to keep inmind that the bundle of His is very susceptible to anytoxic agent; and in those cases where heart-block is dueto some cause other than syphilis, the administration ofan arseno-benzol compound may have a seriously damag-ing effect upon the structure itself. Indeed, as has beenpointed out by Bickel, arsenobenzenes acting upon a myo-cardium damaged by syphilis or any other cause may setup a grave derangement of the conducting function of thebundle. It may actually produce a condition of heart-block where none previously existed. Bismuth or thepentavalent arsenicals are practically free from thisdanger.

(To be continued)

REFERENCESBICKEL. Arch. des mal. du Cceur, des Vaissaux et du Sang, January,

1925, P. 39.BROOKS. Amer. Journ. Med. Sc., I9I3 clxvi., 5I3.DONNISON. Brit. Med. Journ. March gth, I929.HARRIS. Brit. Med. Journ., May igth, I928.IHAZEN. " Syphilis" (2nd Ed.), p. 2II et seq. Henry Kimpton,

London.HEIMANN, STRACHAN and HEYMAN. Brit. Med. Journ., February

23rd, I929.OSLER and GIBSON. "System of Syphilis," I909, iii., P. 27. Power

and Murphy.SAGGIORO. Cuore e Circolazione, April, I924, P. I37.WARTHIN. Amer. Journ. Syph., I9I8, ii., 425.

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